Worldwide, tetanus is still a disease that kills hundreds of thousands each year. Tetanus is currently thought to be a disease that results from the production of toxin in C. tetani contaminated wounds. A pilot study we conducted in germfree rodents demonstrates that C. tetani can grow and produce toxin in the alimentary tract and may pose a heretofore unsuspected threat to newborn infants whose alimentary tract is acquiring a microflora or to adults whose intestinal flora is altered by oral antibiotics. We challenged (oral and intrarectal) germfree mice and rats with spores or vegetative cells of Clostridium tetani. Although C. tetani spores remained viable within the intestinal tract, they were unable to germinate. In contrast, vegetative cells were able to colonize the intestinal tract of mice and rats, replicate, and produce toxin. This intestinal toxicoinfection was lethal for some of the rodents; male mice were the most susceptible and a flaccid paralysis and respiratory arrest (not classic tetanospasm) was observed in moribund animals. Tetanus antitoxin was detected in the sera of monoassociated rats that survived the colonization with C. tetani. Thus, in the absence of microbial competition C. tetani vegetatave cells replicated, caused a toxicoinfection that was lethal for some adult mice and stiumlated the formation of tetanus antitoxin in serum. This study is designed to pursue this new and interesting observation in greater depth and to assess the pathogenesis of intestinal colonization with C. tetani for neonatal, weanling, young adult and aged germfree rodents.